Alzheimer Disease

Chandra RK. · Memorial University of Newfoundland, St. John's, Canada. · Nutrition. · Pubmed #11527656 No free full text.

Abstract: OBJECTIVE: To determine whether supplementation with vitamins and trace elements in modest amounts influences cognitive function in apparently healthy, elderly subjects. METHODS: The study was designed as a randomized, double-blind, placebo-controlled trial. Ninety-six, apparently healthy, independent men and women older than 65 y of age were recruited and randomized to receive a supplement of trace elements and vitamins or a placebo daily for 12 mo. Blood-nutrient levels were estimated at baseline and at the end of the study. The major outcome measure assessed was cognitive function consisting of immediate and long-term memory, abstract thinking, problem-solving ability, and attention. RESULTS: Eighty-six subjects completed the 1-y trial. The supplemented group showed a significant improvement in all cognitive tests (P < 0.001 to 0.05) except long-term memory recall (P > 0.1). Those whose blood-nutrient levels were below the reference standard showed lower responses on cognitive tests. There was no significant correlation between individual nutrient levels and performance on various cognitive function tests. CONCLUSIONS: Cognitive functions improved after oral supplementation with modest amounts of vitamins and trace elements. This has considerable clinical and public health significance. We recommend that such a supplement be provided to all elderly subjects because it should significantly improve cognition and thus quality of life and the ability to perform activities of daily living. Such a nutritional approach may delay the onset of Alzheimer's disease.

Doglio LE, Kanwar R, Jackson GR, Perez M, Avila J, Dingwall C, Dotti CG, Fortini ME, Feiguin F. · Cavalieri Ottolenghi Scientific Institute, Universita degli Studi di Torino, 10043, Orbassano, Torino, Italy. · Neuron. · Pubmed #16675392 No free full text.

Abstract: Genetic analysis of familial Alzheimer's disease has revealed that mutations in the gamma-secretase enzyme presenilin promote toxic Abeta secretion; however, presenilin mutations might also influence tau hyperphosphorylation and neurodegeneration through gamma-secretase-independent mechanisms. To address this possibility and determine whether other components of the gamma-secretase complex possess similar regulatory functions, we analyzed the roles of presenilin, nicastrin, and aph-1 in a Drosophila model for tau-induced neurodegeneration. Here, we show that presenilin and nicastrin prevent tau toxicity by modulating the PI3K/Akt/GSK3beta phosphorylation pathway, whereas aph-1 regulates aPKC/PAR-1 activities. Moreover, we found that these transmembrane proteins differentially regulate the intracellular localization of GSK3beta and aPKC at cell junctions. Inhibition of gamma-secretase activity neither interfered with these kinase pathways nor induced aberrant tau phosphorylation. These results establish new in vivo molecular functions for the three components of the gamma-secretase complex and reveal a different mechanism that might contribute to neuronal degeneration in Alzheimer's disease.

Mandal PK, Pettegrew JW, McKeag DW, Mandal R. · Western Psychiatric Institute and Clinic Department of Psychiatry, University of Pittsburgh Medical School, 3811 O'Hara Street, PA 15213, USA. · Neurochem Res. · Pubmed #16807784 No free full text.

Abstract: Alzheimer's disease (AD) is a significant contributor to cognitive decline and is responsible for about half of the cases of dementia in later life. Although exact etiology of AD is not known, however, many risk factors for AD are identified. Anesthesia for elderly patients is considered as a risk factor in AD as they frequently experience deterioration in cognitive function with long exposure to anesthetics during surgery. Inhaled anesthetic agents remain the mainstay for patients undergoing major surgical operations. This study using multidimensional NMR spectroscopy provides the first direct evidence in vitro that inhaled anesthetic, halothane specifically interacts with Abeta40 and Abeta42 peptide. Halothane induces structural alternation of Abeta peptide from soluble monomeric alpha-helical form to oligomeric beta-sheet conformation, which may hasten the onset of AD. Abeta42 is more prone to oligomerization compared to Abeta40 in the presence of halothane. The molecular mechanism of halothane induced structural alternation of Abeta peptide is discussed.

Hussain HM, Hotopf M, Oyebode F. · No affiliation provided · N Engl J Med. · Pubmed #17251541 No free full text.

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